Cell death plays a central role in a wide variety of liver diseases, is of obvious importance in the reaction of cells to anoxia, and is the major criteria for evaluating the action of chemotherapeutic agents on cancer cells. Such a role for cell death in so many human diseases makes knowledge of its pathogenesis of major importance. Recent work in this laboratory has shown that D-galactosamine-induced liver cell injury has certain features that make it a seemingly analyzable model for the experimental analysis of the molecular mechanisms underlying cell death. Using this system, data has been obtained implicating the plasma membrane and associated changes in cellular calcium levels as a primary event in the sequence of changes leading to liver cell death. Experiments are proposed designed to determine the exact nature of the plasma membrane injury, the mechanism of calcium accumulation and the role of calcium ions in the metabolic deterioration of the liver cells. BIBLIOGRAPHIC REFERENCES: Farber, J.L., El-Mofty, S.K., Aleo, J.J., Schanne, F.A.X., and Serroni, A. Intracellular Calcium Homeostasis in Galactosamine-Intoxicated Rat Liver Cells. Active Sequestration of Calcium by Microsomes and Mitochondria. Arch. Biochem. Biophys. 178: 617-624, 1977.